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We thank Hector Lacassie et al.
for their comments and interest in our recent article1 and are pleased to take this opportunity to reply.

Dr. Lacassie has correctly observed that our study results were different from expectations; we discussed this in our article. It was interesting to note that another minimum local analgesic concentration study authored by Benhamou et al.2 and published in the same issue of the Journal
reported a 19 percent difference in potency in favor of levobupivacaine. This, although not statistically significant, is consistent with Dr. Lacassie’s own motor block potency work.

They also raise the interesting question as to whether the minimum local analgesic concentration method is sufficiently powerful to detect small differences in local anesthetic potencies. In general, the reproducibility across the differing modalities of the minimum local analgesic concentration studies to date has been of great interest. For example, not only did the studies comparing the minimum local analgesic concentration of bupivacaine and ropivacaine find identical analgesic potency ratios of 0.6,3,4 but Dr. Lacassie’s work using relative motor blocking potencies5 returned similar ratios. In addition, the three studies were conducted on three different continents! The crux of the issue is not whether up-down studies are robust enough to detect differences; they clearly have been. It is rather the reliability of the outcome measure of interest, be it analgesia, sensory level, motor block, or toxicity. Clearly analgesia, and to some extent toxicity, is more subjective and in the particular setting of labor, pain is a dynamic process and therefore subject to greater variability. In contrast, motor block and sensory level should be more independent of, for example, the process of labor and therefore may be more robust measures than analgesia. However, as the primary indication for local anesthetics is analgesia, this has to be directly assessed when considering therapeutic benefit.

The third explanation offered by Lasassie et al.
that “the ED50for pain relief…is in the vicinity of the lower end of the dose-response curves of both drugs” needs some clarification. Binary yes/no outcomes occupy individual dose-response distributions. So it follows that there will be a spectrum of curves for the different measured end points and that the ED50for each will be in the steep portion of the curve.

In closing, we agree that further studies are required and that up-down ED50studies have distinct advantages compared with other designs with regard to robustness, whatever the modality being studied. A follow-up study comparing the minimum local analgesic concentrations of bupivacaine, ropivacaine, and levobupivacaine is currently in progress at our institution.